Benign course in multiple sclerosis: a review

Since the 1950s, it has been recognized that a subgroup of multiple sclerosis (MS) patients exists that shows little or no progression in the severity of the disease over time. This group is referred to as 'benign' MS. Although a substantial amount of research in MS indicates a multifactorial background in disease severity, to date it is still difficult to predict whether the course will be benign at onset and it is difficult to find factors that influence the course of the disease over time. Maintaining or restoring neural conduction inside a central nervous system lesion seems to be the essence of staying 'benign'.     

Early prognostic factors for disability in multiple sclerosis, a European multicenter study

The effects of initial clinical variables on short-term prognosis are analyzed in a cross-sectional study of 574 multiple sclerosis patients from 7 centers in 5 European countries. Patients with a primary progressive course had a 2.3 higher mean disability score (EDSS) than the primary remittent group after a mean duration of disease of 6.6 years. High age at onset was associated with a primary progressive course, and was also related to increased risk of a rapid shift to a secondary progressive course. Among the remittent patients without a secondary progressive course a high age at onset was significantly correlated to a higher disability score. In the whole remittent group the presence of pyramidal and cerebellar symptoms at onset predicted both a high disability score and a rapid shift to a secondary progression, while the effect was reverse for sensory and visual symptoms. No difference between the sexes was found.     

Contribution of relapses to disability in multiple sclerosis

The impact of relapses on long-term disability in multiple sclerosis remains unclear; however some evidence suggests that relapses play an important role in determining subsequent prognosis. We report on outcome, prognostic factors for recovery and the contribution of relapses to the accumulation of fixed disability in a large series of patients with documented relapses. Two hundred and seventynine relapses in 182 patients were assessed before, during and after relapse by expanded disability status scale and data analysed to assess degree of recovery. Factors affecting outcome were considered including sex, age and site of relapse. Mean EDSS prior to relapse was 3.73, during relapse 5.18 and post relapse 4.23. Mean interval to post relapse assessment was 127 days post relapse. Mean residual change in EDSS score (pre to post relapse) was 0.50 points. Overall 49.4 % of patients had a residual increase in disability post relapse of at least 0.5 EDSS points and 32.7 % had an increase of at least 1 point. No significant difference was observed in mean residual EDSS for sex, site of relapse or age at relapse or in the proportion of patients with a residual increase in disability of ≥ 1 EDSS point post relapse. 14.4 % of patients had no increase in EDSS score during relapse compared to pre relapse. These results suggest that acute relapses are commonly associated with an objective worsening of disability in the majority of patients with MS and that recovery is incomplete in approximately half and not influenced by gender, age or site of lesion. Therapies which reduce relapse frequency and/or severity might therefore be expected to slow or prevent worsening of disability if initiated prior to the onset of more permanent damage.     

Benign multiple sclerosis

A small fraction of patients with multiple sclerosis (MS) have a benign course of the disease. The definition of benign MS has been heavily weighted towards physical disability and in particular ambulation. However, patients who are fully ambulatory may still be heavily disabled by non-motor symptoms like fatigue, pain, depression and cognitive dysfunction. These non-motor symptoms should be considered when defining benign MS.     

Course and prognosis of chronic progressive multiple sclerosis: Results of an epidemiological study

In studies on the natural course of multiple sclerosis (MS), several forms of the disease are distinguished. The most important are the relapsing remitting and the chronic progressive forms. The relationship between these remains unclear. In a prospective epidemiological survey we studied the course of MS using the year in which the chronic-progressive phase started as a landmark. The reliability of this "year of progression" was examined in an observer agreement study. Data were acquired from 342 patients. Progression of the handicap was most rapid in case of a secondary progressive course, female sex, high relapse rate in the preceding remitting phase and "year of progression" at a higher age. Survival after the "year of progression" was lowest in the secondary progressive group. Determining the "year of progression" seems to be significant for the prognosis.     

ApolipoproteinE epsilon 4 allele is not associated with disease course and severity in multiple sclerosis

Background – No study has assessed the association between apolipoproteinE (APOE) and multiple sclerosis (MS) forms grouped by also taking into account cognitive performance. Aims of the study – To assess the relationship between APOE and disease course, particularly focusing on benign MS (BMS), defined as also including cognitive preservation. Methods – In 173 consecutive patients, we assessed the association between APOE and MS course and severity. Results – Twenty‐nine APOE‐?4 carriers were identified. The ?4 allele was not associated with BMS. Moreover, it was associated neither with other disease courses nor with the time to reach disability milestones and secondary progression. Conclusion – Although plausible, the association between APOE and MS course (particularly with BMS defined by including cognitive preservation) and disease severity remains controversial.     

Clinical characteristics and long term prognosis in early onset multiple sclerosis

The clinical features, disease course and long term prognosis of early onset multiple sclerosis (EOMS) are variable. A preponderance of female sex, a high incidence of visual and brainstem symptoms at onset and a relapsing–remitting disease course with slower progression rate all have been considered relatively frequent in this subgroup of MS patients. Unfortunately, follow–up in previous studies has usually been limited to less than 10 years, precluding general statements on the long term evolution and prognosis in EOMS. In this retrospective study of EOMS with a substantially longer follow–up of 20.8 years, clinical characteristics, disease course and long term prognosis are described in 49 EOMS patients. In a representative subgroup of 28 patients disability was scored using Kurtzke’s Functional System (FS) and Expanded Disability Status Scale (EDSS). The mean period of follow– up for these patients was 28.7 years. The present study confirms that several specific clinical characteristics can be identified in EOMS patients, such as a mainly relapsing–remitting disease onset and frequent presentation with brainstem– cerebellar dysfunction (28.6 %), pyramidal symptoms (18.4 %) and optic neuritis (14.3%). However, after a long period of follow–up the overall disease course and prognosis do not seem to differ from that in adult onset MS. By consequence a young age at onset in MS cannot be considered a favourable prognostic factor.     

Age at onset, initial symptomatology and the course of multiple sclerosis

Analysis of the initial symptomatology, age at onset and course as factors influencing the prognosis of multiple sclerosis (MS) revealed that the rate of deterioration in a sample of 1,571 patients - registered during a neurological examination in a standardized way - was slower for patients with optic neuritis as the initial sign, for patients with an age at onset of under 39 years and for patients with a remissive course of disease.
The progression index, obtained by dividing the present disability by the duration of the disease was used as a measure for the rate of progression.
The course of the disease was responsible for 13% and age at onset for 1.6% of the total variation in the progression index.
Endogenous or exogenous factors may modify the appearance and dynamics of MS which might be a syndrome rather than a disease entity.     

The clinical significance of the neutrophil-to-lymphocyte ratio in multiple sclerosis

Multiple sclerosis (MS) is one of the main chronic inflammatory diseases of the central nervous system that causes functional disability in young people. The aim of this study was to investigate the neutrophil-to-lymphocyte ratio (NLR) in patients with MS and the relationship between the NLR and the severity of the disease. One hundred and two MS patients (31 patients were in relapse; 71 patients were in remission) and 56 healthy controls were included. Complete blood counts as well as demographic and clinical data from MS patients were evaluated retrospectively. The NLRs were calculated for all participants and were compared; the cut-off value was also determined for the NLR and Expanded Disability Status Scale (EDSS). MS patients had a significantly higher NLR (p < 0.001) than the control group. The NLR levels were significantly higher in patients who were in relapse than patients in remission (p = 0.039). The cut-off value for the NLR to predict an MS diagnosis and activity were determined to be 2.04 and 3.90, respectively. The NLRs were directly correlated with erythrocyte sedimentation rate levels (r = 0.795, p < 0.001). Logistic regression analysis with dichotomous EDSS score showed that a high NLR was an independent predictor of the progression of disability. The NLR may be a biomarker that has simple, quick, inexpensive and reproducible properties in MS to predict patient's prognosis.     

Benign multiple sclerosis

Objectives A study of cognitive, psychological and social aspects in benign multiple sclerosis (MS). Methods One hundred and sixty three patients with benign MS (defined as disease duration ≥ 15 years and Expanded Disability Status Scale (EDSS) score ≤ 3.0 ) underwent neuropsychological testing on the Rao’s Brief Repeatable Battery (BRB) and the Stroop test, evaluation of depression on the Montgomery and Asberg Depression Rating Scale (MADRS), of fatigue on the Fatigue Severity Scale (FSS) and of handicap on the Environmental Status Scale (ESS). Patients’ cognitive performance was compared with that of 111 demographically matched healthy controls. Cognitive impairment was defined as the failure in at least 3 tests, using the fifth percentile of controls’ performance as the cut-off point. Clinical correlates of cognitive impairment were determined by multiple logistic regression analysis. Results Cognitive assessment led to the identification of 74 subjects (45%) with cognitive impairment. Significant fatigue was found in 80 subjects (49%) and depression in 88 patients (54%). In comparison with cognitively preserved subjects, cognitively impaired patients exhibited higher handicap scores on the ESS (p = 0.005). In the regression analysis, only EDSS scores were significantly associated with cognitive impairment (OR 1.8, 95%CI 1.2–2.6). Conclusion Current definitions of benign MS may overestimate this entity, since they are mainly weighted for the patients’ motor abilities and fail to capture relevant disease-related cognitive, psychological and social problems. Received in revised form: 24 October 2005     

Prognosis of multiple sclerosis *

Clinical data and the prognosis are presented for an epidemiological group of multiple sclerosis (MS) patients. Symptoms and signs of MS, with the exception of optic nerve involvement, were less frequent in the group of 221 patients from the epidemiological area of Southern Lower Saxony than in the hospital series (n= 1837), although the mean duration of the disease was somewhat longer in the epidemiological group. Fifty-two percent of the latter were unrestricted or minimally restricted upon examination compared to 26% of the hospital group. Taking a progression index as a measure for prognosis (disability grade divided by the duration of the disease) 36% of the epidemiological group belonged to a benign category compared to 16% in the hospital group. The progress of these patients was not more than 1 grade of disability within a 5-year-period (progression index 0.2 or less). A malignant course was defined as a progression of at least 7 grades during a 5-year period (progression index 1.4 or more). Ten percent of the hospital series belonged to this category compared to 2% of the epidemiological group. Thus data from a representative group of patients show that the overall prognosis of MS is considerably better than generally suspected.     

多发性硬化的临床特点与预后的分析

目的分析多发性硬化(MS)的临床特点与预后。方法回顾性分析117例MS患者的临床资料,从临床、影像学等方面对视神经脊髓型(OSMS)和经典MS型(CMS)进行比较。结果117例MS患者中,OSMS型42例(35.9%),CMS型75例(64.1%)。临床表现中,OSMS患者出现肢体无力(88.1%)、感觉缺失(85.7%)、感觉异常(57.1%)、视物模糊(76.2%)、尿便障碍(73.8%)明显多于CMS患者(70.7%、56.0%、20.0%、45.3%及26.7%)(均P<0.05);出现共济失调(7.1%)、复视(0)及构音不清(0)明显少于CMS患者(42.7%、10.7%及16.0%)(P<0.05～0.01)。OSMS患者出现长节段融合性脊髓病变的比例(94.1%)显著多于CMS患者(48.2%)(P<0.01)。脑脊液检查和诱发电位检查结果OSMS组和CMS组差异无统计学意义。发病5年后扩大的残疾状态量表(EDSS)评分OSMS组(2.42±0.90)显著高于CMS组(1.50±0.88)(P<0.05)。在发病的第1年和第3年,年平均复发次数复发缓解型OSMS[(1.92±1.05)次、(1...     

Physical dimension of fatigue correlated with disability change over time in patients with multiple sclerosis

To determine the value of fatigue in predicting the change in disability status in patients with multiple sclerosis (MS), we realized a prospective population-based cohort study of 196 patients with clinically definite MS. In 2002, baseline data were collected on fatigue (Modified Fatigue Impact Scale), health-related quality of life (SF-36), and disability status (EDSS score). The EDSS scores were determined again at least three years later. Univariate and multivariate analysis were performed to determine the predictive value of different dimensions of fatigue and other variables (depression and SF- 36) on the change in disability status. Of the 196 patients, 106 (54%) patients had an unchanged status or improvement and 90 (46%) showed a worsening of disability. After three years, with control for gender, age, and baseline disability status, a high baseline level of physical fatigue was associated with a worsening of disability status, whereas a low baseline level of physical fatigue was associated with the absence of worsening of the EDSS score. Other dimensions of fatigue, depression and SF-36 were not associated with a worsening of disability.A patient's perceived fatigue may be not only a clinically and psychosocially meaningful outcome but also a predictor of objective outcomes such as changes in disability status at three years.     

Epidemiological investigations into multiple sclerosis in Southern Hesse. V. Course and prognosis

Course and possible prognostic predictors were studied retrospectively in 363 MS patients collected during an epidemiological study. The proportion of patients showing a primarily progressive course was 18%; 19% of patients of more than 10 years duration showed a benign course, and 8% of those of less than 16 years duration, a malignant course. Although benign cases were twice as frequent in females as in males, the difference between both sexes was not significant. A primarily or secondarily progressive course, a high number of functional systems involved and cerebellar signs occurring in the course indicated a poor prognosis whereas symptoms at onset, age at onset as such, and occupation were without predictive value. No predictors of a favourable course were found. Of the patients of 11-15 years duration, 17% were confined to a wheelchair, 40% were restricted to a walking distance of 500 metres or less, 61% were unable to work and 45% had urinary incontinence. The corresponding figures for those of 21-25 years duration were 40%, 71%, 76% and 50%.     

T2 lesions and rate of progression of disability in multiple sclerosis

Background and purpose: To assess the predictive value of T2 lesions on the rate of progression of disability in multiple sclerosis (MS). Methods: We reanalyzed T2 lesion number and load on brain MRI scans, performed before 1997, of 186 MS patients, who were clinically followed. There were 90 patients with progressive MS (35 secondary progressive and 55 primary progressive), and 96 with relapsing remitting MS. The rate of progression of disability was measured by time to sustained progression of disability (defined as an increase in ≥ 1 point when the Expanded Disability Status Scale (EDSS) was 5.5 or less and an increase in EDSS of ≥ 0.5 point when the EDSS was 6.0 or higher), and by the Multiple Sclerosis Severity Score (MSSS). Results: During follow‐up (median 15 years, IQR 12–17 years), 94% of the patients with progressive MS and 50% of the patients with relapsing remitting MS had progression of disability. Higher T2 lesion number and load were modestly associated with a higher rate of disease progression on the MSSS and a shorter time to progression of disability in relapsing remitting MS, but not in progressive MS. Conclusions: Our findings indicate that the amount of T2 lesions has a small predictive value for progression of disability in relapsing remitting MS, but has no influence on the rate of progression in progressive MS.